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Several lines of evidence have clearly indicated that inflammation plays a pivotal role in the development of atherosclerosis and of its thrombotic complications such as acute coronary syndromes or ischemic stroke. Thus, it has been postulated that the use of anti-inflammatory agents might be extremely useful to improve cardiovascular outcome. Recently, increasing attention has been reserved to one of the oldest plant-derived drugs still in use in clinical practice, colchicine that has been used as drug to treat inflammatory diseases such gout or Mediterranean fever. To date, current guidelines of the European Society of Cardiology have included colchicine as first line choice for treatment of acute and recurrent pericarditis. Moreover, several studies have investigated its role in the clinical scenarios of cardiovascular disease including chronic and acute coronary syndromes with promising results. In this review, starting from a description of the mechanism(s) involved behind its anti-inflammatory effects, we give an overview on its potential effects in atherothrombosis and finally present an updated overview of clinical evidence on the role of this drug in cardiovascular disease. [ABSTRACT FROM AUTHOR]

The risk of ischemic events carried by different clusters of type 2 diabetes mellitus (DM) in the setting of secondary prevention is not definite and the association between DM and bleeding complications is controversial. We explored these issues in the START-ANTIPLATELET, a multicenter Italian registry including acute coronary syndrome (ACS) patients. Study outcome was 1-year incidence of the net composite endpoint including major adverse cardiovascular events (MACE) or any bleeding and its individual components across different DM strata (no DM, DM with or without insulin). Out of 951 patients, 20.0% had diabetes not on insulin and 2.5% had diabetes on insulin. The rate of the net composite endpoint was highest in patients receiving insulin (39.4 per 100 person-years vs 11.7 in diabetic patients not on insulin vs 14.0 in those without DM; p = 0.007). In DM, the higher risk of MACE was regardless of insulin use (p = 0.36). Conversely, the increase in bleeding complications was limited to patients on insulin (Hazard Ratio 2.31, 95% CI 0.93-5.71 vs no DM; p = 0.0105 across DM strata). On top of aspirin, the rates of the net composite endpoint were similar with ticagrelor/prasugrel or clopidogrel irrespective of DM status (p for interaction 0.63). In conclusion, in ACS patients, type 2 DM enhances the risk of MACE regardless of the DM cluster, whereas the propensity to bleeding related to DM seems confined to insulin-treated patients. [ABSTRACT FROM AUTHOR]

Staging and monitoring of multiple myeloma (MM) is mainly based on monoclonal component quantification; the absence of such a parameter renders difficult follow up of patients with nonsecretory MM (nsMM). In this study our aims were to determine the specificity and sensitivity of Tc99m-sestaMIBI scintigraphy at diagnosis and during follow up of nsMM patients. Nine nsMM patients were prospectively studied at diagnosis and during treatment for a mean time of 33 months (range: 12–65+). Tc99m-sestaMIBI (MIBI) scintigraphy was compared to conventional imaging (CI: X ray with CAT or NMR details) at diagnosis and during follow up. At diagnosis, CI and MIBI were concordant in three patients; CI showed more focal lesions than MIBI in four patients, while MIBI revealed more focal lesions than CI in two patients. During the follow up, MIBI uptake was normal in the four patients who achieved remission. Five patients did not achieve remission: CI and MIBI were concordant in three, while MIBI was falsely negative in two patients. In conclusion, Tc99m-sestaMIBI scintigraphy has high sensitivity (no false positive cases) and 78% specificity (2/9 false negative cases) in tracing active nsMM lesions; it should be considered complementary to CI for monitoring this rare disease. [ABSTRACT FROM AUTHOR]

Focuses on the case report concerning the treatment of multiple myeloma with conventional chemotherapy. Administration of cyclophosphamide pulses in patients with multiple myeloma; Identification of adult age affected by the disease; Response and tolerance of patients to the treatment.

A letter to the editor is presented regarding the treatment of patients with cardiac immunoglobulin light chain (AL) amyloidosis through mobilization of peripheral blood hematopoietic stem cells.

Several scores can predict clinical outcomes of patients with Acute Coronary Syndromes (ACS). The validated PARIS (Patterns of Non-Adherence to Anti-Platelet Regimen in Stented Patients) score is poorly used in clinical practice because it needs items that are not always easily available. The ACEF (Age, Creatinine, and Ejection Fraction) score is more attractive because it only includes three items. We compared these scores to risk-stratify ACS patients enrolled into the START (Survey on anticoagulated pAtients RegisTer)-ANTIPLATELET registry. ACS patients who completed 1-year follow-up (n = 1171) were grouped in tertiles (low, medium, and high-risk) according to their ACEF/PARIS scores. Primary endpoints were: one-year MACCE (major adverse cardiac and cerebrovascular events: death, non-fatal myocardial infarction, stroke or target vessel revascularization) and NACE (net adverse cardiac and cerebrovascular events): MACCE plus major bleeding). MACCE incidence was higher in the high-risk tertile (15%) VS low/medium (3/7 %) risk tertiles (P < .001). NACE incidence in the high-risk tertile was 24% VS low/medium (9/15 %) risk tertiles (P < .001), independently of the risk score used. The ACEF score has similar accuracy as the validated PARIS score for the estimation of ischemic/bleeding risk. Thereby, we strongly suggest its use in clinical practice to risk-stratify ACS patients and select optimal therapeutic strategies. [ABSTRACT FROM AUTHOR]

Abstract: Background: Frequent endocrine disorders have been reported after allogeneic stem-cell transplant, but data on adult survivors of autologous transplants are still scarce. Methods: In this prospective study we investigated early (at 3 months) and late (at 12 months) endocrine dysfunctions in 95 consecutive autologous stem-cell transplant recipients (47 men and 48 women) aged 16 to 55 years. The functions of the hypothalamic-pituitary-gonadal/thyroid/adrenal/somatotroph axis were evaluated. Results: Three months after the transplant, insulin-like growth factor-1 values were below the normal range in 53 patients (56%); 37 of 40 women (93%) of reproductive age experienced precocious ovarian failure; 39 of 46 men (85%) showed high follicular stimulating hormone, and 17 men (37%) showed low testosterone levels. Adrenal insufficiency occurred in 28 patients (30%) during the peritransplant period after corticosteroid withdrawal. Transient subclinical hyperthyroidism was found in 15 patients (16%). Transient “low T3” syndrome was revealed in 29 patients (31%). Twelve months after the transplant, insulin-like growth factor-1 values were still low in 36 patients (38%). Menstrual cycles resumed in four women; follicular stimulating hormone, luteinizing hormone, and estradiol levels improved in 10 patients. Testosterone was low in only two men (4%). Seminal analysis revealed azoospermia in 32 (91%) of 35 men examined. Subclinical hypothyroidism was found in 11 patients (12%); eight of them had previously received radiotherapy for the upper half of the body. Conclusion: This study documents frequent endocrine disorders during the first year after autologous stem-cell transplant. Despite a tendency to improve, in more than half of the cases, the complications persisted for more than 1 year. Therefore, to diagnose and correct early and late endocrine dysfunctions, endocrine screening is required during the first year in all patients undergoing autografting. [Copyright &y& Elsevier]

Background: Thrombosis with cardiovascular involvement is a crucial complication in COVID-19 infection. COVID-19 infects the host by the angiotensin converting enzyme-2 receptor (ACE2r), which is expressed in endothelial cells too. Thus, COVID-related thrombotic events might be due to endothelial dysfunction. IL-6 is one of the main cytokines involved in the COVID-19 inflammatory storm. Some evidence indicates that Vitamin D (VitD) has a protective role in COVID-19 patients, but the molecular mechanisms involved are still debated. Thus, we investigated the effect of VitD on Tissue Factor and adhesion molecules (CAMs) in IL-6-stimulated endothelial cells (HUVEC). Moreover, we evaluated levels of the ACE2r gene and proteins. Finally, we studied the modulation of NF-kB and STAT3 pathways., Methods: HUVEC cultivated in VitD-enriched medium were stimulated with IL-6 (0.5 ng/mL). The TF gene (RT-PCR), protein (Western blot), surface expression (FACS) and procoagulant activity (FXa generation assay) were measured. Similarly, CAMs soluble values (ELISA) and ACE2r (RT-PCR and Western blot) levels were assessed. NF-kB and STAT3 modulation (Western blot) were also investigated., Results: VitD significantly reduced TF expression at both gene and protein levels as well as TF-procoagulant activity in IL-6-treated HUVEC. Similar effects were observed for CAMs and ACE2r expression. IL-6 modulates these effects by regulating NF-κB and STAT3 pathways., Conclusions: IL-6 induces endothelial dysfunction with TF and CAMs expression via upregulation of ACE2r. VitD prevented these IL-6 deleterious effects. Thus, it might be speculated that this is one of the hypothetical mechanism(s) by which VitD exerts its beneficial effects in COVID-19 infection.

Women undergoing stem cell transplantation (SCT) are mostly young and have more than 90% probability of ovarian failure, which is often permanent. A woman's age, use of radiotherapy and alkylating chemotherapy, and the allogeneic type of transplant are associated with a higher rate of premature ovarian failure and worse residual ovarian function. Premature ovarian failure has serious systemic and psychological effects that may need treatment and should be managed by practitioners trained to treat this particular population of women. Ultrasonographic evidence of ovarian follicles is often associated with a future resumption of cycles, but there are no serum markers to predict the return of ovarian function in these patients. In our center, the rate of ovarian function recovery was 7% after allogeneic SCT and 25% after autologous SCT (P<0.05). There are no guidelines on how to manage premature ovarian failure induced by myeloablative treatments followed by SCT. Because of the likelihood of the need for long-lasting estrogen plus progestin therapy (EPT) and the increased risk of secondary neoplasia after SCT, the EPT should be as physiological as possible. In our experience, the cyclical sequential combination of estradiol (2 mg daily) plus dydrogesterone (10 mg for 14 d/mo) was associated with excellent compliance because of its simple administration and few adverse effects. Such a treatment led to a dramatic improvement in vasomotor, urogenital, and psychological symptoms related to estrogen deficiency. However, in the allogeneic transplantation setting, up to 25% of women may suffer from gynecological chronic graft-versus-host disease, which may become apparent as hematocolpometra after introduction of EPT. Thus, accurate pretreatment evaluation and frequent monitoring during treatment are required. Moreover, EPT absorption may be reduced in patients who received allotransplants and have gastrointestinal or skin chronic graft-versus-host disease.

Background: Increased serum leptin has been described after various organ transplants, with a mechanism that is still unclear., Methods: We measured serum leptin in 60 patients before and after allogeneic (allo) or autologous (auto) stem cell transplant (SCT) and in 60 healthy controls, matched for age and body mass index (BMI)., Results: Serum leptin was higher in patients after SCT than before and in controls. Leptin production was higher after allo- than after auto-SCT; the presence of chronic graft-versus-host disease (cGVHD) was associated with the highest values. The physiological correlation with BMI was lost in the allogeneic setting, indicating a strong influence of factors other than the nutritional status on circulating leptin. No relationship was found between serum leptin levels and time from transplant, age, cortisol, C-reactive protein, and T-lymphocyte CD4-to-CD8 ratio. Among the cytokines secreted by type-1/type-2 T-helper lymphocytes, only serum interferon-gamma significantly correlated with serum leptin levels. Anti-leptin blocking antibodies partially inhibited T-cell activation in mixed lymphocyte reaction, suggesting a link between leptin and T-lymphocyte activation in the allo-SCT setting., Conclusion: Taken together, these findings suggest that increased serum leptin concentrations may contribute to T-cell activation during development of cGVHD.

Background and Objectives: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is widely used to mobilize peripheral blood stem cells (PBSC) for autologous or allogeneic transplants. Such treatment may cause spleen enlargement; exceptionally, spontaneous spleen rupture has been reported. We investigated changes in spleen size during stem cell mobilization., Design and Methods: We evaluated spleen size, comparing palpation with ultrasound (US)-evaluated longitudinal diameter and volume, in 13 healthy donors and 22 patients with a hematological malignancy who were undergoing PBSC mobilization with rhG-CSF-including regimens., Results: Intraobserver and interobserver variability of US-calculated spleen volume was very low; the correlation between the volume calculated by US and that measured by 3-dimensional computed tomography was excellent. During mobilization, spleen enlargement was detected by palpation in 17% of subjects, by US-measured longitudinal diameter in 60%, and by US-calculated volume in 91%. The median increase in spleen volume was 300 mL (range, 54-820; p<0.001) in healthy donors and 135 mL (range, 0-413; p=0.004) in the group of patients; the enlargement correlated with white blood cell count elevation (p=0.016) but not with circulating CD34+ cells. One month after the last administration of rhG-CSF, the median decrease was 160 mL (range, 35-800) in healthy donors and 58 mL (range, 0-310) in patients., Interpretation and Conclusions: When evaluated by sensitive methods, rhG-CSF caused spleen enlargement in almost all individuals treated. US-calculated volume proved to be an excellent method, much better than longitudinal diameter, for detecting non-palpable splenomegaly induced by rhG-CSF.

Background: The most debilitating skeletal complication of stem cell transplantation (SCT) is avascular necrosis (AVN)., Methods: Two hundred seven consecutive patients were evaluated prospectively for AVN. They survived disease free for more than 180 days after autologous or allogeneic SCT for hematologic malignancies. The diagnosis of AVN in suspicious cases was confirmed by magnetic resonance imaging. Possible correlations with treatments, bone mineral density (BMD), graft versus host disease (GVHD), and in vitro growth of fibroblast progenitors were investigated. Bone mineral density was evaluated by dual-energy X-ray absorptiometry in 100 transplanted patients, and the in vitro growth of fibroblast progenitors was monitored by a fibroblast colony-forming unit (CFU-F) assay in 30 patients after allogeneic SCT., Results: Twelve patients developed AVN 3-114 months (median, 26 months) following SCT: 10 (10%) after allogeneic SCT and 2 (1.9%) after autologous SCT (P = 0.04). Twenty-five joints were affected by AVN. All patients had femoral head involvement, which was managed with hip replacement in six of them. All but one patient who developed AVN after allogeneic SCT suffered from chronic GVHD (cGVHD). Avascular necrosis occurred 1-4 months after exacerbation or progression of cGVHD. Cumulative dose of steroids was similar in both SCT groups (including steroids given pretransplant for the basic disease), whereas treatment duration was significantly longer in the allogeneic SCT group. Avascular necrosis was related to the decreased number of bone marrow CFU-F colonies in vitro, but not to BMD values., Conclusions: Avascular necrosis is a skeletal complication that occurs more often after allogeneic than after autologous SCT. Occurrence of AVN symptoms after clinical follow-up of cGVHD suggests that cGVHD requiring long-term steroid therapy is one of the main risk factors for AVN. Avascular necrosis may be facilitated by a severe deficit in the repopulating capacity of bone marrow stromal stem cells after SCT., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11373)

Background and Objectives: The optimal method for liver biopsy in patients with simultaneous bone marrow and liver impairment has not yet been established. New approaches (e.g. imaging-guided methods) for this procedure are needed. In spite of coagulopathy, immunosuppression, anemia or ascites, we histologically characterized liver damage in a series of bone marrow transplanted patients using color-Doppler ultrasonography, which permits very keen visualization (and assessment) of hepatic parenchyma and vessels, and a fine needle for percutaneous biopsy., Design and Methods: We performed percutaneous liver biopsy using a Menghini-type automatic very fine cutting needle (1.2 mm, 18G) under color ultrasound guidance in 16 bone marrow transplanted adult patients consecutively seen in our units from 1998 to 2001. The patients had clinically defined diffuse serious liver damage; liver biopsy was performed between 3 and 10 months after allogeneic (n= 11) or autologous (n= 5) transplantation., Results: Fifteen patients tolerated the procedure well and had no discomfort, while one patient developed intrahepatic hemorrhage. All liver biopsies were suitable for histologic examination and informative, revealing the specific etiology of liver damage: graft-versus-host disease in six patients, drug toxicity in five, hepatitis C virus acute reactivation in two, and in one each vanishing bile duct syndrome, nodular regenerative hyperplasia and hemochromatosis. Biopsy detected potentially injurious concomitant factors, e.g., occult intrahepatic hepatitis B virus infection and reactivation. Histology radically changed the presumptive clinical diagnosis in 10 of the 16 patients and led to successful treatment changes in six., Interpretation and Conclusions: Percutaneous biopsy with a small cutting needle under color ultrasound guidance carries a low risk of complications and provides reliable information regarding liver histology in critically ill patients, in the early stage after bone marrow transplantation. We suggest including this imaging-guided mini-invasive procedure to the standard work-up of post-transplant liver damage.

The authors report 20 cases of medullary thyroid carcinoma over the period from 1980 to 2000. Two patients turned out to be inoperable and 18 patients underwent total thyroidectomy, associated with dissection of the central lymphatic compartment in 5 patients and with dissection of the central and lateral lymphatic compartments in 10 patients with clinical or instrumental evidence of cervical lymphadenomegaly. Serum calcitonin levels proved to be a reliable marker for the diagnosis of persistence or recurrence of the disease. The follow-up, lasting from 1 to 208 months, demonstrated that in 7 cases in which serum levels of calcitonin underwent normalization there was no recurrence of disease. Among 11 cases with persistence of high calcitonin levels, 6 died and only 2 presented no evidence of metastases. On the basis of our analysis of the cases reported, total thyroidectomy associated with dissection of the central lymphatic compartment is an adequate treatment for patients in stages I and II. The authors regard routine dissection of the lateral lymphatic compartment as unadvisable.